1) An ectopic pregnancy occurs when a fertilized egg implants outside of the uterus, usually in the fallopian tubes. Risk factors include prior pelvic infection, surgery on the fallopian tubes, prior ectopic pregnancy, IUD use, DES exposure, and assisted reproduction. 2) In a tubal pregnancy, the fertilized egg implants and develops in the fallopian tube. This is not viable and can lead to tubal rupture due to the thin tube wall. 3) Without treatment, outcomes of tubal ectopic pregnancy include tubal mole, abortion, or rupture.

1. AREZ ESMAIL QADR SHAMAL M. AZIZECTOPICPREGNANCY

2. Normal pregnancy implantationPregnancy is the period during which a woman carries a developing fetus normally in the uterus, starting from conception (fertilization of ova) until the baby born.After ovulation the ovum is picked up by thefimbria of fallopian tubes and then swept by ciliary action towards the ampulla where fertilization occurs. As soon as the zygote develops it begins dividing very rapidly, it remains in the fallopian tube for 3 -4 days untill reaches morula stage (8-32 cell stage)

3. Normal pregnancy implantationThe embryo proceeds through the isthmus to the uterine cavity for up to 72 hours, by the sixth day it enters the uterus and begins to penetrate the decidua (endometrium) this is called implantation which takes place within the uterine cavity in normal positioned pregnancy . Then hCG is produced by trophoblast, which can be detected in the serum of the mother in the first week after implantation, its level doubles every 36-48 hours in normal healthy pregnancy starting from 5 to 50 ,100, till reaching 1000 IU/LDelay or obstruction of the passage of fertilized egg down the fallopian tube to the uterus may result in implantation in the fallopian tube or ovary or peritoneal cavity, this known as ectopic pregnancywhich eventually most fails to develop , and the hCG fails to raise dramatically as happens in the normal intra uterine pregnancy.

4. Normal pregnancy implantation

5. Ectopic pregnancy ?

6. Ectopic pregnancy Definition: An ectopic pregnancy, or eccysis , is a complication of pregnancy Occurs when the site of implantation is outside of the womb (uterine cavity) either in the tubes,ovaries or abdominal cavity, With rare exceptions, ectopic pregnancies are not viable, Pregnancy can even occur in both the womb and the tube at the same time (heterotopic pregnancy).Classification:1- tubal pregnancy: The vast majority of ectopic pregnancies 95-98 % implant in the Fallopian tube, among these: 80% in the ampulla 10% in isthmus 5 % in fimbria 2% interstitial 2% in a rudimentary horn of a bicornuate uterus

7. classification2-Nontubal ectopic pregnancy Rare sites (2-5%) are; The ovaries, broad ligaments, Abdominal cavity and peritoneum cervix. 3-Heterotopic pregnancy in rare cases of ectopic pregnancy 1/1000, there may be two fertilized eggs, one outside the uterus and the other inside. This is called a heterotopic pregnancy. Often the intrauterine pregnancy is discovered later than the ectopic, mainly because of the painful emergency nature of ectopic pregnancies.

8. classification Since ectopic pregnancies are normally discovered and removed very early in the pregnancy, an ultrasound may not find the additional pregnancy inside the uterus. When hCG levels continue to rise after the removal of the ectopic pregnancy, there is the chance that a pregnancy inside the uterus is still viable. This is normally discovered through an ultrasound Although rare, heterotopic pregnancies are becoming more common, likely due to increased use of IVF.

9. Common sites for ectopic pregnancy

10. epidemiologyIncidence; 22/1000 live births16/1000 pregnanciesIn USA from 1970 – 1992 , the risk 5x increased from 4 to 19 / 1000 pregnancies fatality rate :fatality rate from ectopic pregnancies dropped almost 90% (from 35.5 per 1000 ectopics to 3.8 per 1000 ectopics).Despite the sharp improvement in the fatality rate by the end of this period of time, ectopics were still the second leading cause of maternal mortality in the USA (accounting for 12% of all maternal deaths in 1987).

11. Why? The reason for the increase in ectopic pregnancy during this time period is not entirely clear, but it was thought that the increase of risk factors were responsible for a significant portion of the increased number of cases of ectopic pregnancy.

12. Risk factorsAny mechanism that interferes with the normal function of fallopian tube increases the risk of ectopic pregnancyThe mechanism canbe:Anatomical; scarring that blocks transport of the eggFunctional; impaired tubal mobility

14. Risk factors1-History of pelvic infectionPID is the most common risk factor for ectopic pregnancy8 folds increases the risk, due to destruction of the fallopian tubes. Chlamydia (a common sexually transmitted disease) and Gonorrhea are both able to grow within the fallopian tubes and cause; 1-tremendous damage to the endosalpinx (lining of the inner tubal lumen), 2-agglutination (sticking together) of the mucosal folds in the tube 3-peritubal adhesions (scar tissue). . the risk of an ectopic pregnancy is greater when the woman with the infection is younger Other pelvic or lower abdominal infections can also result in pelvic adhesions and an increase in the ectopic pregnancy rate (such as appendicitis).The chances of another ectopic in the same fallopian tube also in the other tube are increased 5x

15. Risk factors2-History of surgery on the fallopian tubes or within the pelvis:Tubal ligation in the past 2 years,When a bilateral tubal ligation (tubes tied) is followed by either an unexpected pregnancy (failed tubal ligation) or is "reversed" with a tubal reanastomosis (tubal reconstruction) there is an increased risk of a tubal ectopic pregnancy. When a woman has a history of pelvic surgery that is associated with significant adhesion formation (such as myomectomy) there is also an increased risk of an ectopic pregnancy.

16. Risk factors3- Prior history of ectopic pregnancy. When an ectopic pregnancy in the fallopian tube is treated conservatively (by preserving the tube), there is a roughly 10 fold increase the risk of recurrence in the same tube4-History of IUD use. The use of an IUD is a classic "risk factor" for ectopic pregnancy. Actually, all but the progesterone containing IUDs are relatively protective against ectopic pregnancy while the IUD is in place. That is, the number of ectopic pregnancies in women using an IUD for contraception is about one half that of women using no contraception. However, of IUD pregnancies there is a greater chance of an ectopic location (3-4%) since the number of intrauterine pregnancies with an IUD in place is markedly reduced.

17. Risk factorsAdditionally, IUDs can be associated with infections of the uterine cavity and fallopian tubes (especially just after insertion) which can independently increase the chance for an ectopic pregnancy..The reason for this increase in the nomber of EPs with progesterone IUD is not clear. A theory is that somehow the progesterone enhances tubal implantation.

18. Risk factors5-History of Diethylstilbestrol (DES )exposure in utero. This drug is a is a synthetic nonsteroidal estrogen that was used for certain conditions, including breast and prostate cancers ,From about 1940 to 1970, DES was given to pregnant women under the mistaken belief it would reduce the risk of pregnancy complications and losses Later researches has shown that this drug has many bad medical effects and female babies of women who used it were at risk of developmental abnormalities of the genital systemTheir tubes are more likely to be abnormal and predispose to ectopic pregnancy, these females were known as DES daughters

19. Risk factors6-History of destruction of the uterine cavity or lining. Such as history of uterine synechiae (scar tissue) from previous surgery (like endometrial ablation for dysfunctional bleeding ) or presence of multiple submucosal fibroid tumors this cause a larger percentage of the pregnancies to implant in a space other than the uterine cavity. Similar to the situation with IUDs, the total ectopic pregnancy rate may not be increased but when a pregnancy does occur the reduced likelihood of an intrauterine pregnancy increases the relative percentage of ectopic pregnancies.

20. Risk factors7-History of non-infectious pelvic inflammation (endometriosis, foreign body). Inflammation of the delicate tubal structures can result in adhesion formation (scar tissue), which will then increase the risk of an ectopic pregnancy. This inflammation may be due to endometriosis or the presence of a foreign body, either of which are strongly associated with scar tissue formation.

21. Risk factors8-Use of assisted reproductive technology (such as IVF (in vetro fertilization) and GIFT (gamete intrafallopiantransfere). When multiple embryos or gametes are placed into the uterus or the fallopian tubes, the risk for multiple pregnancy rises significantly. The risk of twins and heterotopic pregnancy is generally thought to be about 1 / 30,000 pregnancies .with ARTs the rates of ectopics and dizygotic twins have increased to 1/10,000 .the incidence of heterotopic pregnancy may increase to as frequently as 1 /100 pregnancies.

22. Tubal pregnancy

23. Pathophysiology The trophoblast develops in the fertilized ovum and invades deeply into the tubal wall. Following implantation, the trophoblast produces hCG which maintains the corpus luteum. The corpus luteumproduces oestrogen and progesterone which change the secretoryendometrium into decidua. The uterus enlarges up to 8 weeks and becomes soft. The tubal pregnancy does not usually proceed beyond 8-10weeks due to: > lack of decidual reaction in the tube, > the thin wall of the tube, > the inadequacy of tubal lumen, > bleeding in the site of implantation as trophoblast invades.

24. PathophysiologySeparation of the gestational sac from the tubal wall leads to its degeneration, and fall of hCG level, regression of the corpus luteum and subsequent drop in the oestrogen and progesterone level.This leads to separation of the uterine decidua with uterine bleeding.Fate of tubal pregnancyTubal moleTubal abortion Tubal rupture

25. Fate of tubal pregnancy1- Tubal mole: The gestational sac is surrounded by a blood clot and retained in the tube.This may remain for long period in the tube and forms so called (chronic ectopic pregnancy),or they may be gradually absorbed (involution)2-Tubal abortion:This occurs more if ovum had been implanted in the ampullary portion of the tube. Separation of the gestational sac is followed by its expulsion into the peritoneal cavity through the tubal ostium.Rarely, reimplantation of the conceptus occurs in another abdominal structure leads to secondary abdominal pregnancy.

26. Fate of tubal pregnancyIf expulsion was complete the bleeding usually ceases but it may continue due to incomplete separation or bleeding from the implantation site.

27. Fate of tubal pregnancy3-Tubal rupture:More common if implantation occurs in the narrower portion of the tube which is the isthmus.Rupture may occur in the anti-mesenteric border of the tube. Usually profuse bleeding occurs -> intraperitonealhaemorrhage.If rupture occurs in the mesenteric border of the tube, broad ligament haematomawill occur.

28. presentationEarly symptoms are either absent or subtle. Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of 5 to 8 weeksThe most common presenting symptoms that are suggestive for EP are:

29. Clinical traid (3As)Amenorheaectopic pregnancyAbdominal pain Abnormal vaginal bleeding

30. symptomsPain and discomfortIn the Lower back , abdomin, or pelvis.Usually unilateral Pain may be confused with a strong stomach pain, it may also feel like a strong crampShoulder pain. This is caused by free blood tracking up the abdominal cavity and irritating the diaphragm, and is an ominous sign.Pain while urinatingPain while having a bowel movement

31. symptomsBleedingVaginal (external)bleeding usually mild. An ectopic pregnancy is usually a failing pregnancy and falling levels of progesterone from the corpus luteum on the ovary cause withdrawal bleeding. Internal bleeding (hematoperitoneum) is due to hemorrhage from the affected tube.Dizziness, headache, weakness, fainting all may happen due to bleeding

32. signsGeneral examination: signs of early pregnancy (Breast tenderness, nausea and vomitig, change of apettite …) Weakness, pallor, hypotension and tachycardia, tachypnoea due to bleedingAbdominal examination: Lower abdominal tenderness and rigidity especially on one side may be present.

33. signsVaginal examination: Vaginal spotting Bluish vagina and bluish soft cervix. Uterus is slightly enlarged and soft. Marked pain in one iliac fossa on moving the cervix from side to side. Ill defined tender mass may be detected in one adnexa in which arterial pulsation may be felt.Speculum or bimanual examination should not be performed unless facilities for resuscitation are available, as this may induce rupture of the tube

34. diagnosisThe diagnosis can be difficultYour doctor may perform some tests to help confirm suspected ectopic pregnancy including;Detailed history of (cycle, pregnancy, PID,infertility, gynaecological surgery, contraception…)Proper general, abdominal, vaginal examination and vital signsInvestigations: including

35. Diagnosis1.hormonal assaySerum β-hCGUrine pregnancy tests are positive in only 50-60% of ectopic. Detection of β-hCG in the serum by ELISA or radioimmunoassay are more sensitive and can detect very early pregnancy about 10 days after fertilization i.e. before the missed period.If the test is negative (generally less than 5 IU/L), normal and abnormal pregnancy including ectopic are excluded. If the test is positive , and doubles every 36-48 hour till reaching 1500 IU/L which is The threshold of discrimination for intrauterine pregnancy, this indicates a normal intrauterine pregnancy, An abnormal rise in blood β-hCG levels may indicate an ectopic pregnancy and ultrasonography is indicated.

36. DiagnosisProgesteroneThe second most common hormone after hCG in pregnancy is progesterone. Generally, a progesterone concentration of greater than 25 ng/mLis highly correlated with a normal intrauterine pregnancy while a concentration of less than 5 ng/mLis highly correlated with an abnormal and nonviable pregnancy

37. Diagnosis2-UltrasoundIn general, a positive β-hCG test with empty uterus by sonar ± adnexial mass indicates ectopic pregnancy.Discriminatory hCG zones: Diagnosis of ectopic pregnancy is made if there is:An empty uterine cavity by abdominal sonography with b -hCG value above 6000 mIU/ml.An empty uterine cavity by vaginal sonography with b -hCG value above 2000 mIU/ml.

38. Ultrasound

39. Diagnosis3-Culdocentesisin this test, a needle is inserted into the space at the top of the vagina, behind the uterus and in front of the rectum to aspirate fluid andDetermines if there is blood in the space behind the uterusIf non-clotting blood is aspirated from the Douglas pouch , intraperitonealhaemorrhage is diagnosed. But if not, ectopic pregnancy cannot be excluded.

40. Diagnosis4-laparoscopy or laparotomycan also be performed to visually confirm an ectopic pregnancy. Often if a tubal abortion or tubal rupture has occurred.Laparoscopy: an endoscope is inserted through a small incision in the woman’s abdomenThis allows you to see the fallopian tubes and other organsThis takes place in an operating room with anaesthesia

41. Uncommon Sites of Ectopic Pregnancy1-Cornual angular pregnancy2-Pregnancy occurs in the blind rudimentary horn of a bicornuate uterus.3-Cervical pregnancy4-Ovarian pregnancy5-Abdominal (peritoneal) pregnancy

42. Cornual angular pregnancy It is implantation in the interstitial portion of the tube.It is uncommon but dangerous because when rupture occurs bleeding is severe and disruption is extensive that needs hysterectomy.In some cases, the pregnancy is expelled into the uterus and rupture does not occur. www.freelivedoctor.com

43. Pregnancy in a rudimentary horn Pregnancy occurs in the blind rudimentary horn of a bicornuate uterus. As such a horn is capable of some hypertrophy and distension, rupture usually does not occur before 16-20 weeks.

44. Cervical pregnancy Implantation in the substance of the cervix below the level of uterine vessels.May cause severe vaginal bleeding. Can be diagnosed by trans vaginal ultrasound

45. Ovarian pregnancyAetiology: * Pelvic adhesions.* Favourable ovarian surface for implantation as in ovarian endometriosis.Pathogenesis: * Fertilization of the ovum inside the ovary or, * implantation of the fertilized ovum in the ovary.

46. Ovarian pregnancySpiegelberg criteria for diagnosis of ovarian pregnancy:* The gestational sac is located in the region of the ovary,* the ectopic pregnancy is attached to the uterus by the ovarian ligament, * ovarian tissue in the wall of the gestational sac is proved histologically, * the tube on the involved side is intact.www.freelivedoctor.com

47. Abdominal (peritoneal) pregnancyTypes:Primary: implantation occurs in the peritoneal cavity from the start.Secondary: usually after tubal rupture or abbortion.Intraligamentous pregnancy: is a type of abdominal but extraperitoneal pregnancy. It develops between the anterior and posterior leaves of the broad ligament after rupture of tubal pregnancy in the mesosalpingeal border or lateral rupture of intramural (in the myometrium) pregnancy.

48. Abdominal (peritoneal) pregnancyDiagnosis:History: of amenorrhoea followed by an attack of lower abdominal pain and slight vaginal bleeding which subsided spontaneously. Abdominal examination: Unusual transverse or oblique lie.Foetal parts are felt very superficial with no uterine muscle wall around.Vaginal examination: The uterus is soft, about 8 weeks and separate from the foetus. No presenting part in the pelvis.

49. Abdominal (peritoneal) pregnancySpecial investigations:Plain X-ray: shows abnormal lie. In lateral view, the foetus overshadows the maternal spines .Ultrasound: shows no uterine wall around the foetusMagnetic resonance imaging (MRI): has a particular importance in preoperative detection of placental anatomic relationships. www.freelivedoctor.com

50. DIFFERENTIALDDXDIAGNOSIS

51. (1) NON GYNECOLOGICAL

52. (2) Gynecologic disorders

53. TREATMENTRxEctopic

54. Treatment options

55. EXPECTANTMANAGEMENT

56. Criteria for selectionasymptomatic women no evidence of rupture or hemodynamic instabilityless than 100 ml fluid in the pouch of DouglashCG less than 1000 iu/l at initial presentation Adnexalmass less than 3cmthey should objective evidence of resolution, such as decliningbhCG levels.They must be fully compliant and must be willing to accept the potential risks of tubal rupture.

57. MONITORINGInitial follow up twice weekly with serial hCGmeasurementsweekly by transvaginal examinationsBy the first weekdrop in HCG levelAdnexal mass sizeOtherwise reassess the options (Medical/Surgical)If the fall of HCG & reduction in size of adnexal mass satisfatoryweekly hCG and transvaginal ultrasound examinationsTill the HCG falls less than <20 IU

58. 45–70% of pregnancies of unknown location resolve spontaneously with expectant managementEctopic pregnancy was subsequently diagnosed in 14–28% of cases of pregnancy of unknown locationIntervention has been shown to be required in 23–29% of cases.

59. MEDICAL2MANAGEMENT

60. CRITERIA for MEDICAL MANAGEMENTSelection criteriaMinimal symptoms & The patient must be hemodynamicallystableno signs or symptoms of active bleeding or haemoperitoneum.Absence of foetal heart beatNormal FBC,U&E(urea & electrolytes),LFT(liver function tests)Exclusion criteriaAny hepatic dysfunction, thrombocytopenia (platelet count <100,000), blood dyscrasia(WCC <2000 cells cm3).Difficulty or unwillingness of patient for prolonged follow-up (average follow-up 35days).Ectopic mass >3.5cm The presence of cardiac activity in an ectopic pregnancy

62. METHOTREXATEMethotrexate – a drug that destroys actively growing tissues such as the placental tissues ,is used as an injection in selected cases to avoid surgery (in non ruptured ectopic) Side effects include abdominal pain for 3 – 7 days in 50% of cases and mild symptoms of nausea, mouth dryness and soreness and diarrhoea,Methotrexate-Intramuscular(buttock or lateral thigh)Dose calculated from body surface areaUsual dose ranges between 75-95 mgHCG checked on day 4 & day 7If fall is less than 15 % consider second dose of methotrexateAnti-D should also be given if required

63. Rest up to one hour after the injection.

64. Check for any local reaction.

65. ADVICESPatient should be given information on(preferably written)Need for further treatmentAdverse effectsWomen should be able to return easily for assessment at any time during follow-upAdviceavoid sexual intercourse during treatment to maintain fluid intake use reliable contraception for three months after methotrexate has been given, barrier or hormonal)Avoid exposure to sunlight.“- Avoid alcohol and vitamin preparations containing folic acid until the hormone level is back to zero. - Avoid aspirin or drugs such as Ibuprofen for one week after treatment.

66. OUTCOME90% successful treatment with single dose regime.Recurrent ectopic pregnancy rate 10 – 20%.Tubal patency approximately 80%.14 % of medical management second dose of methotrexate75% would experience abdominal pain-separation pain. This usually occurs between day 3-710% would finally require surgical management

67. COST BENEFITScheap in the initial period

68. but considering the cost of follow up & the loss of work time for patient & carers

69. no cost saving was seen at serum hCG levels above 1500 IU/l due to the increased need for further treatment and prolonged follow-up.3SURGICALMANAGEMENT

70. Indications for surgical treatmentThe patient is not a suitable candidate for medical therapy.Medical therapy has failed.The patient has a heterotopic pregnancy with a viable intrauterine pregnancy.The patient is hemodynamically unstable and needs immediate treatment.

71. EMERGENCY

72. RUPTUREDECTOPICPREGNANCY

73. Get help- call senior /Consultant on call ABC of resuscitation give facial oxygenSite two IV lines , commence IV fluids (crystalloid) Send blood for FBC, Clotting screen and cross-match at least 4 units of blood.insert indwelling catheterarrange theatre for laparotomywhilst awaiting transfer to theatre continue fluid resuscitation and ensure intensive monitoring of haemodynamic statedo not wait for BP and pulse to normalise prior to transfer-resuscitation and surgery need to go hand in hand.Pfannensteilincision, salpingectomy and wash out of abdomenassess bloods /consider CVPrecord operative findings including the state of the remaining tube/pelvis Anti – D immunoglobulin (250 IU)to be given to Rhesus negative women

74. LaparascopyORlaparatomy??Laparoscopy has become the recommended approach in most cases.Laparotomy is usually reserved for patients: who are hemodynamically unstable

75. patients with cornual ectopic pregnancies.

76. for surgeons inexperienced in laparoscopy and in patients where laparoscopic approach is difficult

78. SalpingectomyORSalpingotomy ??SalpingectomySalpingectomy (tubal removal) is the principle treatment especially where there is tubal ruptureSalpingotomyConservative surgical management may be employed when the ectopic has not ruptured and where the tube appears normalTotal salpingectomy is the procedure of choice: In a patient who has completed childbearing and no longer desires fertility

79. in a patient with a history of an ectopic pregnancy in the same tube.

80. in a patient with severely damaged tubes,

81. Persistent trophoblastWhen salpingotomy is done, protocols should be in place for the identification and treatment of women with persistent trophoblast.Monitoring serum HCG levels would help to identify the persistent trophoblast.Most Easily Treated With MTX

82. Other TypesMxCervical OvarianHeterotropicAbdominal

83. Cervical pregnancy

84. Ovarian pregnancyLaparotomy and inoculation of the ectopic pregnancy and reconstruction of the ovary if possible. Otherwise, removal of the affected ovary is indicated.Ovarian cystectomy is the preferred treatment Treatment with MTX and prostaglandin injection has also been reported

85. Abdominal (peritoneal) pregnancyThe condition should be terminated surgically through Laparotomy once diagnosedMTX treatment appears to be contraindicated because of the high rate of complications due to rapid tissue necrosis

86. Heterotropic pregnancyDepends upon the state of the woman and the skill of the doctor..Surgical

87. Laparoscopy is the ideal surgical method to remove an ectopic pregnancy before it ruptures without interrupting the viable pregnancy. Although the intrauterine pregnancy can still survive if the ectopic pregnancy ruptures, there is an increased danger of miscarriage. The surgery must be done with great skill and it is important that bleeding be addressed quickly. Medical therapies include injecting the ectopic pregnancy in order to terminate the gestation.

88. Anti DNon sensitized women who are rhesus negative with a confirmed or suspected ectopic pregnancy should receive anti-D immunoglobulin.In accordance with RCOG Guideline it is recommended that anti-D immunoglobulin at a dose of 250 IU (50 micrograms) be given to all non sensitized women who are rhesus negative and who have an ectopic pregnancy.

89. ADVICENot using IUCDNot using progesterone only pillsTreatment for any PIDFollow up by HCG that should disappear after 1 monthDo HSG after 40 day to see patency of the tubeUse barrier method of contraceptionTiming of pregnancy, visit specialist in any missed period